Abstract
The effects of duration in culture were assessed in mesangial cells from theH-2K b-tsA58 transgenic mouse using the whole-cell configuration of the patch clamp technique.The whole-cell potassium conductance remained constant in cells from passages 8–17 while the chloride conductance was found to decrease in cells after passage 15. This reduction of the chloride conductance, indicating cell dedifferentiation, was the result of complete loss of the calcium-activated component of the conductance and loss of part of the calcium-insensitive component. Insulin, which increases the calcium-sensitivity of the calcium-activated component of the chloride conductance in early passage cells, restored part of the calcium-sensitive component of the chloride conductance in dedifferentiated cells. Vasoactive agonists such as arginine vasopressin and angiotensin II stimulate a chloride-dependent depolarization in mesangial cells that initiates cell contraction. In view of the importance of the chloride flux it is possible that the loss of a significant magnitude of chloride conductance may underlie mesangial cell pathology to some degree. This is supported by data that show insulin can reverse many of the early renal changes observed in diabetic nephropathy and, as shown in this study, that insulin enhances the chloride conductance in dedifferentiated, cultured mesangial cells.
References
Bank N, Lahorra MA, Aynedjian HS (1987) Acute effect of calcium and insulin on hyperfiltration of early diabetes. Am.J.Physiol 252: E13-E20
Barber RD, Woolf AS, Henderson RM (1995) A characterization of the chloride conductance in mesangial cells from the H-2Kb-tsA58 transgenic mouse. Biochim.Biophys.Acta 1269: 267–274
Chambers TJ, Owens JM, Hattersley G, Jat PS, Noble MD (1993) Generation of osteoclast-inductive and osteoclastogenic cell lines from the H-2Kb-tsA58 transgenic mouse. Proc.Natl.Acad.Sci.(USA) 90: 5578–5582
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch. 391: 85–100
Jat PS, Noble MD, Ataliotis P, Tanaka Y, Yannoutsos N, Larsen L, Kioussis D (1991) Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58 transgenic mouse. Proc.Natl.Acad.Sci.(USA) 88: 5096–5100
Kreisberg JI (1982) Insulin requirement for contraction of cultured rat glomerular mesangial cells in response to angiotensin II: Possible role for insulin in modulating glomerular hemodynamics. Proc.Natl.Acad.Sci.(USA) 79: 4190–7192
Ling BN, Seal EE, Eaton DC (1992) Regulation of mesangial cell ion channels by insulin and angiotensin II. Possible role in diabetic glomerular hyperfiltration. J.Clin.Inv. 92: 2141–2151
Mené P, Simonson MS, Dunn MJ (1989) Physiology of the mesangial cell. Physiol.Rev. 69: 1347–1424
Author information
Authors and Affiliations
Additional information
An Erratum for this article can be found at http://dx.doi.org/10.1007/BF03036363
Rights and permissions
About this article
Cite this article
Barber, R.D., Henderson, R.M. Insulin restores the calcium-activated chloride conductance in dedifferentiated renal glomerular mesangial cells from theH-2K B-TSA58 transgfenic mouse. Pflügers Arch. 432, 749–751 (1996). https://doi.org/10.1007/s004240050194
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s004240050194